▎ WuXi AppTec content team editor
Recently, the top academic journal Nature published an important paper on CAR-T therapy. A team led by Professor Carl June, a world-renowned car-T therapy expert, has found through long-term research that the effects of CAR-T therapy can last up to 10 years! "Based on these results, we can now conclude that CAR-T therapy can really cure cancer patients." Professor June said.
To understand the study, we have to start with two patients more than a decade ago. In the summer of 2010, bill Ludwig and Doug Olson both struggled with chronic lymphocytic leukemia. They have received a lot of treatment before and have almost lost the treatments that can be used. It is also with the attitude of a dead horse as a live horse doctor, they participated in the clinical study of CAR-T therapy. It's a very novel technology, and no one knows if it will work. Fortunately, after receiving treatment, both patients' conditions were well controlled within a year. Their treatment stories have also made headlines in the global media, heralding the advent of a new anti-cancer therapy. Today, several CAR-T therapies have been approved around the world, and thousands of people have been treated.
As with any innovative therapy, time is limited and little is known about the long-term efficacy of CAR-T therapy. Chronic lymphocytic leukemia in these two patients is an extremely difficult disease to cure. Although CAR-T therapy can help them alleviate their condition in the short term, can this effect last for life? To answer this question, the researchers continued to take blood samples from the two patients after treatment, trying to see if CAR-T cells would change in the human body — unlike traditional small molecule drugs or biological antibody drugs, CAR-T therapy uses living cells. After entering the patient's body, these cells continue to survive. They are not static, they are constantly evolving.
After a decade without cancer, Doug Olson (center) celebrates his 75th birthday with his family (Credit: Penn Medicine)
In the study, the scientists first confirmed that CAR-T cells were still present in patients ten years after treatment. This may also explain why, ten years after treatment, their condition is still under stable control.
Interestingly, the composition of these cells has changed significantly over time. In the early stages of treatment, CAR-T cells are predominantly CD8-positive T cells. They have a lethal effect, can kill cancerous cells, and treat cancer. But after a few years, most of the CAR-T cells turned CD4-positive. These cells are generally referred to as "helper T cells" and play a major role in assisting and guiding. In two patients, CD4-positive T cells can account for 97-99% of the years after receiving treatment.
The researchers note that this change suggests the role of two types of cells at different stages of treatment: the former is responsible for killing cancer cells, and the latter is responsible for long-term control of the disease. Therefore, long-term cancer control requires a combination of many different cell types. In addition, these results once again prove that CAR-T cells can survive in the human body for a long time.
Schematic diagram of long-term onset of CAR-T therapy (Source: Reference[1])
The researchers also found that a group of T cells expressed neither CD4 nor CD8. They are called gamma-delta T cells. At present, scientists are still studying the specific role of such cells, and many pharmaceutical companies have reached research and development cooperation to develop therapies based on such cells.
"The long-term remission of these patients is impressive, these patients can survive cancer-free, and it is also a great proof of the effectiveness of this 'living drug' in treating cancer," first author J. Professor Joseph Melenhorst said, "Seeing these patients respond well to these innovative cell therapies and spend more time with loved ones is worth all our efforts. ”
Neither has had a recurrence of cancer since they were treated in 2010. Doug Olson runs regularly and completes six half marathons. Bill Ludwig traveled the country with his family and saw the birth of grandchildren. In 2021, he died of COVID-19.
Bill Ludwig (left), the first patient to receive CAR-T therapy, poses with Professor Carl June (Image source: References[2]; Credit: Penn Medicine)
Going forward, scientists hope these insights will help develop better CAR-T therapies. "Many insights will further adjust the way cancer patients receive CAR-T therapy. We also look forward to the next phase of research and improvement on how to better treat other cancers and diseases with CAR-T therapy." Professor June, head of the study, said.